Review: 150 refs.

Abstract:Halting the tumor initiation process by targeting the inhibition of the carcinogens metabolic activators (CYP), the induction of the carcinogen detoxification enzymes (glutathione-S-transferases, GSTs), and the induction of antioxidant activity is an effective strategy. Since several dihydropyrimidine derivatives (Biginelli compounds) are therapeutically active, the present study aimed to synthesize some dihydropyrimidines with multifunctional aromatic substitutions and to investigate their effects as anti-initiating agents. Twelve compounds were synthesized and structurally elucidated. The results revealed that compound 10 was a non-cytotoxic inhibitor of cytochrome P 450 1A (Cyp1A) activity, inducer of GST activity, scavenger of OH and inhibitor of DNA fragmentation. Compounds 1 and 9 were radical scavengers of OH and inhibitors of DNA fragmentation. On the other hand, all compounds were not toxic against different tumor cells, except compounds 2, 4, and 5 possessed non specific cytotoxicity against both liver and colon carcinoma cells, while 7 possessed specific cytotoxicity only against colon carcinoma cells. Compound 1 was a non-cytotoxic inducer of GST activity, scavenger of OH and ROO, and inhibitor of DNA fragmentation. The present study proved that compounds 10 and 1 were active and safe tumor anti-initiating and multi-potent blocking agent.

Different substituents were introduced in positions 2 and 6 of 2,6 diaminopyridine in order to obtain new heterocyclic compounds. A new series of aza pyridine, imidazopyridine, benzodiazepine, indole, pyrimidine, and benzimidazole heterocyclic derivatives were synthesized in good yields. The anticancer activities of some of the new compounds were evaluated against liver cancer cell line HEPG2. Compounds 3, 4, 10, 11, 12, and 17 showed the highest activity when compared to 5-flurouracil (5-FU) and doxorubicin (DOX) chemotherapy.

Some of Schiff base derivatives were separated by condensing 3-formyl-2-quinolinone with various primary amine derivatives in ethanol, in which water is expelled. Moreover, substituted acryloylphenyliminomethylquinolinone chalcone derivatives were prepared by the process of condensation reaction of aldehyde derivatives with 3-acetylphenylquinolinone in dilute solution of ethanolic sodium hydroxide via Claisen-Schmidt condensation method.Cyclization reaction of the quinolinone chalcones with malononitrile, phenylhydrazine, urea and thiourea were also investigated. The structures of these compounds have been elucidated on the bases of spectral data. The novel products were also evaluated for their antimicrobial activity.